Nephron Function and Regulation

Thiazide Diuretics and Calcium Reabsorption

  • Thiazide diuretics block the sodium chloride cotransporter.
  • Less sodium coming down its concentration gradient.
  • Less sodium drives less sodium to come down concentration gradient.
  • Less sodium drives less calcium to come out of the cell.
  • Blocking sodium chloride cotransporter speeds up reabsorption of calcium.
  • Less calcium in the urine; potentially more calcium in the blood.
  • Patients may be hypocalciuric or hypercalcemic.
  • Thiazide diuretics used for stone formers to reduce calcium in urine.

Collecting Duct Cells

  • Two cell types: principal cells and intercalated cells.

Principal Cells

  • Sodium-potassium ATPase pump.
  • Epithelial Sodium Channel (ENaC).
  • Sodium enters cell down concentration gradient via ENaC.
  • Potassium secretion.

Intercalated Cells

  • ATPase pump secretes hydrogen into the lumen.

Ion Movement

  • Sodium enters the cell down its concentration gradient.
  • Negative charge drives potassium and hydrogen ions into the lumen.

Aldosterone

  • Drives processes in both principal and intercalated cells.
  • Renin -> Angiotensin -> Angiotensin II -> Aldosterone.
  • Promotes sodium reabsorption.
  • Promotes potassium excretion.
  • Promotes hydrogen ion secretion.

Impact of Issues in Loop of Henle and Distal Convoluted Tubule

  • Hypokalemia and metabolic alkalosis.
  • Extra sodium in collecting duct leads to more sodium reabsorption.
  • Increased potassium and hydrogen secretion.
  • Can be due to extra sodium flow or sodium and water loss, activating the renin-angiotensin-aldosterone system.
  • Diuretics blocking channels or transport issues lead to hypokalemia (potassium loss in urine) and metabolic alkalosis (hydrogen ion loss in urine).
  • 2-3% sodium reabsorption in cortical collecting duct; significant for fine-tuning.
  • Accompanied by chloride reabsorption, potassium excretion, and acid secretion.
  • All processes stimulated by aldosterone.

Urine Concentration and Dilution

  • Segment permeable to water; permeability determined by antidiuretic hormone.
  • Lumen has negative potential difference.
    • Facilitates chloride movement between cells.
    • Facilitates potassium and hydrogen ion secretion.

Blocking Sodium Reabsorption at ENaC Channel (Amiloride)

  • Salt wasting and hypovolemia due to lack of sodium reabsorption.
  • Hypotension.
  • Hyperkalemia (no potassium secretion).
  • Metabolic acidosis.
  • Renal tubular acidosis type IV (resistance to aldosterone).
  • Or, issue with hydrogen ion pump -> renal tubular acidosis type I (distal renal tubular acidosis).

Impaired Hydrogen Ion Transport

  • Renal tubular acidosis type I (distal renal tubular acidosis).

Enhanced Sodium Transport (Extra Aldosterone or Overdrive ENaC)

  • Think about the resulting presentation.

Nephron Transport Processes

Proximal Tubule

  • Reabsorbs 66\% of sodium and water.
  • Reabsorbs organics and bicarbonate via sodium reabsorption.

Thick Ascending Limb

  • Transports 20\% of sodium.
  • Reabsorbs potassium, calcium, and magnesium (K+ and Mg2+ most regulated).

Distal Tubule

  • Reabsorbs 6\% of sodium.
  • Calcium reabsorption.

Cortical Collecting Duct

  • Fine-tuning of sodium, potassium, and acid-base balance.

Regulatory Mechanisms

  • Next topic: regulating sodium transport; linked to other ion transport.
  • Why reabsorb more or less sodium?
  • What regulatory mechanisms exist?